Article thumbnail

Impact of lenalidomide dose on progression-free survival in patients with relapsed or refractory multiple myeloma

By M A Dimopoulos, M Hussein, A S Swern and D Weber


This analysis assessed the effect of lenalidomide on progression-free survival (PFS). Patients with relapsed or refractory multiple myeloma (RRMM) who received lenalidomide plus dexamethasone in the MM-009 and MM-010 trials were pooled and those who had not progressed and were still receiving lenalidomide at 12 months were included. The median follow-up of surviving patients was 48 months. Of 353 patients who received lenalidomide plus dexamethasone, 116 (33%) had not progressed. Overall, 52 patients (45%) had no dose reductions, 25 (22%) had dose reductions ⩾12 months and 39 (34%) had dose reductions before 12 months. Patients who had dose reductions ⩾12 months had a significantly longer median PFS than those who had reductions before 12 months (P=0.007) or no dose reductions (P=0.039) (not reached vs 28.0 vs 36.8 months, respectively). In a multivariate Cox regression model, dose reduction ⩾12 months was an independent predictor of improved PFS (hazard ratio, 0.47; 95% confidence interval, 0.23–0.98) after adjusting for patient characteristics. The data suggest that to achieve maximum PFS benefit, patients with RRMM should be treated for ⩾12 months with full-dose lenalidomide plus dexamethasone. Thereafter, patients may benefit from lower-dose continued therapy; prospective studies are needed to confirm these findings

Topics: Original Article
Publisher: Nature Publishing Group
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (2006). A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood
  2. (2002). Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood
  3. (2010). Better quality of response to lenalidomide plus dexamethasone is associated with improved clinical outcomes in patients with relapsed or refractory multiple myeloma. Haematologica
  4. (2007). Dexamethasone dose adjustments seem to result in better efficacy and improved tolerability in patients with relapsed/ refractory multiple myeloma who are treated with lenalidomide/ dexamethasone (MM009/010 sub-analysis). Blood
  5. (2010). Dexamethasone synergizes with lenalidomide to inhibit multiple myeloma tumor growth, but reduces lenalidomide-induced immunomodulation of T and NK cell function. Curr Cancer Drug Targets
  6. (1999). Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha.
  7. (2007). Dmoszynska A et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma.
  8. (2011). Effects of lenalidomide and dexamethasone treatment duration on survival in patients with relapsed or refractory multiple myeloma treated with lenalidomide and dexamethasone. Clin Lymphoma Myeloma Leuk
  9. (2006). Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications. Blood
  10. (2011). How ‘immunomodulatory’ are IMIDS? Blood
  11. (2003). Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo. Leukemia
  12. (2002). Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood
  13. (2005). Immunomodulatory drug lenalidomide (CC-5013, IMiD3) augImpact of lenalidomide in relapsed/refractory myeloma MA Dimopoulos et al Leukemiaments anti-CD40 SGN-40-induced cytotoxicity in human multiple myeloma: clinical implications. Cancer Res
  14. (2008). Improved survival in multiple myeloma and the impact of novel therapies. Blood
  15. (2008). Lenalidomide for the treatment of B-cell malignancies.
  16. (2007). Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America.
  17. (2010). Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol
  18. (2009). Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia
  19. (2010). Maintenance treatment with lenalidomide after transplantation for MYELOMA: final analysis of the IFM 2005-02. Blood
  20. Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical implications.
  21. Optimizing the use of lenalidomide in relapsed or refractory multiple myeloma: consensus statement. Leukemia
  22. (2005). Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro. Microvasc Res
  23. (2007). Pharmacokinetics of lenalidomide in subjects with various degrees of renal impairment and in subjects on hemodialysis.
  24. (2004). Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers.
  25. Phase III intergroup study of lenalidomide versus placebo maintenance therapy following single autologous hematopoietic stem cell transplantation (AHSCT) for multiple myeloma: CALGB 100104. Blood 2010; 116: (abstract 37).
  26. Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma.
  27. (2010). SEER data submission, posted to SEER website,
  28. (2010). Single agent lenalidomide in newly diagnosed multiple myeloma: a retrospective analysis. Leukemia Lymphoma
  29. (2003). Thalidomide and a thalidomide analogue drug costimulate virus-specific CD8+ T cells in vitro.
  30. (2001). Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood
  31. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy.
  32. (2002). Thalidomide and its analogues have distinct and opposing effects on TNF-alpha and TNFR2 during co-stimulation of both CD4+ and CD8+ T cells. Clin Exp Immunol
  33. The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions.
  34. The evolution of thalidomide and its IMiD derivatives as anticancer agents.
  35. (2011). The immunostimulatory effect of lenalidomide on NK-cell function is profoundly inhibited by concurrent dexamethasone therapy. Blood